Human papillomavirus (HPV) is the central cause of invasive cervical cancer (ICC) in women, and other anogenital cancers, including anal, penile, vaginal and vulvar cancers. Public health intervention strategies are needed to reduce the genital acquisition of high-risk HPV types to prevent these cancers that affect women and men. Given that men are important in transmitting HPV to their female sexual partners, interventions that reduce HPV acquisition and persistence in men could be an important HPV prevention strategy benefiting both men and women. Limited cross-sectional data suggest that male circumcision may reduce the carriage of penile HPV infection. However, proof that male circumcision reduces HPV penile infection acquisition and/or persistence can only be obtained through the conduct of a prospective, randomized clinical trial (RCT). The University of North Carolina, in collaboration with the UNIM (Universities of Nairobi, Illinois and Manitoba Reproductive Health Project) Male Health Clinic, The University of Illinois at Chicago, the University of Nairobi, the Albert Einstein College of Medicine in New York City, and the Vrije Universiteit Medical Center in Amsterdam proposes to study of the effect of male circumcision on the risk and natural history of penile HPV infection in young, sexually active men in Kisumu, Kenya. This proposed study of penile HPV infection is nested within an ongoing "parent" RCT to assess the effect of male circumcision in reducing HIV incidence in 18-24 year-old men in Kisumu that began in February 2002. This HPV project proposes to determine the type-specific HPV DNA prevalence in penile exfoliated cell samples currently being collected as part of the ongoing RCT of male circumcision. An estimated 2,442 men are expected to contribute penile exfoliated cell specimens from two anatomical sites (the shaft and glans/coronal sulcus). These sample are being collected at enrollment and at the 6-, 12-, 18- and 24- month follow-up visits. Specimens will be tested using a sensitive PCR assay to detect a wide-range of HPV DNA types. HPV viral load of samples positive for HPV types 16, 18, 31, 33 and 45 will be determined using a real-time PCR. A new clinical examination (a visual inspection with 3% acetic acid and aided magnification) will be added to this ongoing RCT at the final 24-month visit to determine the presence of penile lesions (i.e., flat lesions, papular lesions, or condolymata acuminate). Study results will provide the most definitive evidence to date regarding the effect of male circumcision on HPV infection and penile lesions in men. If male circumcision is found to be effective and safe in reducing HPV infection or penile lesions in men, it could in turn reduce HPV prevalence and associated cervical neoplasia in women.